The Cho Lab focuses on a particular type of immune cell: CD8+ T lymphocytes. These white blood cells begin life as naïve T cells, each capable of recognizing a highly-specific protein pattern on invading pathogens. Upon encountering their target, naïve T cells activate, quickly transforming into effector T cells and rapidly proliferating to eliminate the target antigen. Relatively short-lived, most effector T cells undergo the self-elimination process of apoptosis once the target antigen has been removed. But a small subset remains and transforms into memory T cells. Memory T cells protect the organism from the same target over time, thereby laying the foundation of adaptive immunity.
For decades, immunotherapy research has focused on effector T cells as the primary weapon against cancer given their ability to rapidly recognize, proliferate and attack their target. In addition, large numbers of effector T cells can be isolated and expanded from tumor-infiltrating lymphocytes — immune cells that have moved from the blood into tumors — and infused back into patients. This form of treatment is known as adoptive cell transfer (ACT) immunotherapy, and it can be dramatically effective for some patients and some types of cancer. But the treatment is complex, and the clinical results have been inconsistent.
Our very early work looking at the impact cancer has on immune cell physiology led us to the discovery that within a living organism with cancer, developing cancers have the ability to specifically impact and inhibit all phases of the CD8+ T cell lifecycle, with one notable exception: memory T cells. The discovery that memory T cells are not inhibited or suppressed by cancer led us to a new hypothesis: Perhaps these cells, rather than effector T cells, should be the focus of adoptive immunotherapy. But how to isolate and expand large numbers of memory T cells — present in very small concentrations — as well as learning how memory T cell-based adoptive immune therapy might be used synergistically with other forms of immunotherapy and cancer treatments has not yet been fully explored.